Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug

• Published in: Journal of controlled release Vol. 162; no. 3; pp. 561 - 567
• Main Authors: Carlyle, Wenda C., McClain, James B., Tzafriri, Abraham R., Bailey, Lynn, Zani, Brett G., Markham, Peter M., Stanley, James R.L., Edelman, Elazer R.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 28-09-2012; Elsevier
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacokinetics; Biological and medical sciences; coatings; Constriction, Pathologic - drug therapy; Constriction, Pathologic - pathology; coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - pathology; Crystalline; Crystallization; Drug Delivery Systems; Drug-Eluting Stents; drugs; General pharmacology; inflammation; Lactic Acid - chemistry; Medical sciences; Modeling; Models, Biological; Neointima - drug therapy; Neointima - pathology; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetic; pharmacokinetics; Pharmacology. Drug treatments; PLGA; Polyglycolic Acid - chemistry; polymers; Polymers - chemistry; Sirolimus; Sirolimus - administration & dosage; Sirolimus - chemistry; Sirolimus - pharmacokinetics; Stent; Swine; toxicity; Tunica Media - drug effects; Tunica Media - pathology; PLGA; Sirolimus; Stent; Modeling; Crystalline; Pharmacokinetic; Antineoplastic agent; Pharmaceutical technology; Crystalline polymer; Drug carrier; Glycolic acid polymer; Macrolide; Lactone polymer; Macrocycle; Antibiotic; Lactic acid polymer; Aliphatic polymer; Protein synthesis inhibitor; Copolymer; Immunosuppressive agent; Pharmacokinetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.07.004

Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-powder electrostatic process. The AC-SES demonstrated enhanced drug stability under simulated use conditions and consistent drug delivery balanced with coating erosion in a porcine coronary implant model. The initial drug burst was eliminated and drug release was sustained after implantation. The coating was absorbed within 90days.
Following implantation into porcine coronary arteries the AC-SES coating is distributed in the surrounding intimal tissue over the course of several weeks. Computational modeling of drug delivery characteristics demonstrates how distributed coating optimizes the load of drug immediately around each stent strut and extends drug delivery between stent struts. The result was a highly efficient arterial uptake of drug with superior performance to a clinical bare metal stent (BMS). Neointimal thickness (0.17±0.07mm vs. 0.28±0.11mm) and area percent stenosis (22±9% vs. 35±12%) were significantly reduced (p<0.05) by the AC-SES compared to the BMS 30days after stent implantation in an overlap configuration in porcine coronary arteries. Inflammation was significantly reduced in the AC-SES compared to the BMS at both 30 and 90days after implantation.
Biocompatible, rapidly absorbable stent coatings enable the matching of drug release with coating erosion and provide for the controlled migration of coating material into tissue to reduce vicissitudes in drug tissue levels, optimizing efficacy and reducing potential toxicity.
Absorbable coating‐sirolimus eluting stent results in coating deployment following implantation and efficient transfer of drug to tissue. [Display omitted]